Research Article Details

Article ID: A24076
PMID: 23260104
Source: J Pediatr
Title: Alterations in ventricular structure and function in obese adolescents with nonalcoholic fatty liver disease.
Abstract: OBJECTIVE: To determine the association among nonalcoholic fatty liver disease (NAFLD), metabolic function, and cardiac function in obese adolescents. STUDY DESIGN: Intrahepatic triglyceride (IHTG) content (magnetic resonance spectroscopy), insulin sensitivity and &#946;-cell function (5-hour oral glucose tolerance test with mathematical modeling), and left ventricular function (speckle tracking echocardiography) were determined in 3 groups of age, sex, and Tanner matched adolescents: (1) lean (n=14, body mass index [BMI]=20&#177;2 kg/m2); (2) obese with normal (2.5%) IHTG content (n=15, BMI=35&#177;3 kg/m2); and (3) obese with increased (8.7%) IHTG content (n=15, BMI=37&#177;6 kg/m2). RESULTS: The disposition index (&#946;-cell function) and insulin sensitivity index were &#8764;45% and &#8764;70% lower, respectively, and whole body insulin resistance, calculated by homeostasis model of assessment-insulin resistance (HOMA-IR), was &#8764;60% greater, in obese than in lean subjects, and &#8764;30% and &#8764;50% lower and &#8764;150% greater, respectively, in obese subjects with NAFLD than those without NAFLD (P<.05 for all). Left ventricular global longitudinal systolic strain and early diastolic strain rates were significantly decreased in obese than in lean subjects, and in obese subjects with NAFLD than those without NAFLD (P<.05 for all), and were independently associated with HOMA-IR (&#946;=0.634). IHTG content was the only significant independent determinant of insulin sensitivity index (&#946;=-0.770), disposition index (&#946;=-0.651), and HOMA-IR (&#946;=0.738). CONCLUSIONS: These findings demonstrate that the presence of NAFLD in otherwise asymptomatic obese adolescents is an early marker of cardiac dysfunction.
DOI: 10.1016/j.jpeds.2012.11.024

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S01 Improve insulin resistance insulin sensitizer; insulin resistance; glucose tolerance Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

Diseases ID DO ID Disease Name Definition Class
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details
I14 9970 Obesity An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D248 Obeticholic Acid Chemical drug DB05990 NR1H4 activator; NR1H4 agonist; FXR agonist Enhance lipid metabolism Approval rejected Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details